Method for treating libido disorders

ABSTRACT

A method for temporarily enhancing libido in animals comprising administering to an animal an effective amount of a dopamine blocking compound and optionally administering simultaneously or concurrently an effective amount of a noradrenaline potentiating compound.

United States Patent [191 American Drug Index, 1969, p. 448.

Fuxe 5] Nov. 4, 1975 METHOD FOR TREATING LIBIDO Chem. 'Abst. 1 53- 14352c, 1959 DISORDERS Chem. Abst. 2 62-5770H, (1965). [75] Inventor: Kjell Fuxe, SoIIentuna, Sweden [73] Assignee: Nelson R & Development Primary Examiner-Stanley J. Friedman Co., Irvine, Cahf. Attorney, Agent, or Firm-Martin A. Voet [22] Filed: June 3, 1974 2i A N .147 7 1 pp 0 5 85 [57] ABSTRACT 52 11.5. CI. 424/267; 424/319; 424/330 A method for temporarily enhancing libido in animals 51] Int. cl. ..A61K3l/135;A61K31/l95; comprising administering to an animal an effective 5 31/445 amount of a dopamine blocking compound and op- [58] Field of Search 424/330, 267 tivnally administering Simultaneously or concurrently an effective amount of a noradrenaline potentiating '[56] References Cited Compound- OTI-IER PUBLICATIONS 2 Claims, No Drawings METHOD FOR TREATING LIBIDO DISORDERS BACKGROUND OF THE INVENTION 1. Field of the Invention The invention generally relates to a method for enhancing libido.

2. Background of the Prior Art Libido is a medical term for sexual desire. Aphrodisiacs are drugs which enhance libido, that is, arouses the sexual instinct. Aphrodisiacs are used commercially for breeding purposes. Various libido disorders exist in map and include frigidity and impotance.

SUMMARY OF THE INVENTION It would be desirable to have a composition useful as DETAILED DESCRIPTION OF THE INVENTION Compounds which block dopamine in the central nervous system include pimozide, fluspririlene and spiroperidol, all of which compounds are known, e.g. Cuttings Handbook of Pharmacology, 5th ed.

Compounds which potentiate noradrenaline in the central nervous system include amphetamines such as, for example, Benzedrine (amphetamine sulfate), Dexedrine (dextroamphetamine sulfate), Methedrine (methamphetamine hydrochloride) and Fenfluramine; levodopa, adamantin, piperoxan, pemaline, tranylcypromine and especially the enantiomer of tranylcypromine, aletamine, amphonelic acid, cypenamine, encyprate, femcamfamin, fenozalone, fenmetramide, prolintane HCl, rolicyprine, thozolinone and zylofuramine, all of which compounds are known, e.g, Cuttings Handbook of Pharmacology, 5th ed.

The amount of dopamine blocking compound and noradrenaline potentiating compound which may be used in the present invention each varies from about 0.05 mg to about 500 mg/kg and preferably from about 1 mg to about 250 mg/kg per day, bearing in mind, of course, that in selecting the appropriate dosage in any specific case, consideration must be given to the patients weight, general health, metabolism, age and other factors which influence response to the drug. The compounds may be administered in combination or concurrently. That is,'the compounds may be given together in one formulation or may be given at about the same time in separate formulations.

While applicant does not rely on the following theory, it is applicant's belief that the composition of the present invention simultaneously inhibits dopamine and potentiates noradrenaline in the central nervous system and that this action results in an enhanced libido.

As used herein, the term animals refers generally to warm blooded animals and especially domesticated and commercial animals, and includes humans.

The pharmaceutical compositions may be in the form suitable for oral use, for example, as tablets, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide a pharmaceutically elegant and palatable preparation. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for manufacture of tablets. These excipients may be, for example, inert diluents, for example calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example maize starch, or alginic acid; binding agents, for example starch, gelatine or acacia, and lubricating agents, for example magnesium stearate or stearic acid. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period.

Formulations for oral use may also be presented as hard gelatine capsules wherein the active ingredient is mixed with an inert solid diluent, for example calcium carbonate, calcium phosphate or kaolin, or as soft gelatine capsules wherein the active ingredient is mixed with an oil medium, for example arachis oil, liquid paraffin or olive oil;

Aqueous suspensions contain the active ingredients in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example sodium carboxymethyl cellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents may be a naturally-occurring phosphatide, for example lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol, for example polyoxyethylene sorbitol monooleate, or condensation product of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyoxyethylene sorbitan monooleate. The said aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl, p-hydroxy benzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose, saccharin, or sodium or calcium cyclamate.

Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example, sweetening, flavoring and coloring agents, may also be present.

Syrups and elixirs may be formulated with sweetening agents, for example glycerol, sorbitol or sucrose. Such formulations mayfalso contain 'a demulcent, a preservative and flavoring and coloring agents. The pharhours before observation. (c) Chlorpromazine, 5 mg/kg (s.c.) 90 minutes before observation. (d) D- amphetamine sulphate, 3 mg/kg (s.c.) 90 minutes after pimozide or 60 minutes after Spiroperidol or chlormaceutical compositions may be in the form ofa sterile 5 promazine, Le. 30 minutes before observation. (e) injectable preparation, for example as a sterile injecta- Parachlorophenylalaninc-methyl ester HCl (PCPA- ble aqueous suspension. This suspension may be formumethyl ester HCl), 150 mg/kg base (s.c.) 2-4 hours; lated according to the known art using those suitable 26-28 hours; 50-52 hours before observation. (f) Aldispersing or wetting agents and suspending agents pha-methyl-p-tyrosine (AMPT), 100 mg/kg (s.c.) 2-4 which have been mentioned above. The sterile injectahours before observation. ble preparation may also be a sterile injectable solution Behavioral observations were made by placing each or suspension in a non-toxic parenterally-acceptable female with 2 cage-adapted, sexually experienced diluent or solvent, for example as a solution in 13- males for a 5-minute period during which about 20 butane diol. mounts occurred. The following measures were re- The pharmaceutical compositions may be tableted or 15 corded: 1. Proportion of mounts by the male which otherwise formulated so that for every 100 parts by elicited a lordosis response L/M; 2. Lordosis.intenweight of the composition there are present between 5 sity measured on a 3 point scale; 3. Lordosis duration and 95 parts by weight of the active ingredient and (in seconds); 4. Female acceptance ratio No. of preferably between 25 and 85 parts by weight of the acmounts No. of refused mounting attempts mounts, tive ingredient. The dosage unit form will generally a measure of the females willingness to accept the contain between about 100 mg. and about 500 mg. of male when he attempts to mount her. the active ingredient of the formula stated above. As seen from Table 1, pimozide, a potent dopamine From the foregoing formulation discussion, it is ap- (DA) receptor blocking agent, caused a significant inparent that the compositions of this invention can be crease in all measures of the females sexual behavior, administered orally or parenterally. The term parenbut particularly in the mean duration of lordosis reteral as used herein includes subcutaneous injection, sponses (Table 1). These effects were enhanced by a intravenous, intramuscular, or intrasternal injection or noradrenaline potentiator, D-amphetamine. Spiroperiinfusion techniques. 7 dol, a DA receptor blocker, in combination with am- This invention is further demonstrated by the followphetamine produced effects similar to those with ing examples in which all parts are by weight. pimozide/amphetamine.

Table l Effects of various pharmacological agents on the sexual receptivity of estrogen-treated female rats (L/M No. of lordoses No. of mounts'by male; Ll lordosis intensity; LD lordosis duration in seconds; AR acceptance ratio). Values are median Isemiquartile deviation. Statistical analysis, treatment vs. control, Mann-Whitney 'U' test. ns not significant; x p 0.05; xx p 0 xxx p 0.00l

Treatment N L/M L1 LD AR Pimozide 10 0.66 I 0.05 1.94 0.05' 2.00 I 033* 0.95 I 0.05 Control 5 0.27 I 0.25 1.50 I 0.11 0.60 I 0.04 0.78 I 0.12 Pimozide Amphetamine 10 0.84 I 0.10 1.88 I 0.09" 2.08 I 0.31"" 1.00 I 0.02"" Control 5 0.27 I 0.25 1.50 I 0.11 0.60 I 0.04 0.78 I 0.12 Spiroperidol Amphetamine 10 0.86 I 0.16" 2106 I 0.15 1.68 I 0.34 1.00 I 0.02- Control 5 0.11 I 0.13 1.57 I 0.09 0.55 0.02 0.87 I 0.07 tx-methyl-p-tyrosine 10 0.68 I 0.05 2.00 I 0.06 1.22 I 0.28" 0.76 I 0.09" Control 5 0.11 I 0.13 1.57 I 0.09 0.55 I 0.02 0.87 I 0.07 Chlorpromazine Amphetamine 10 0.00 I 0.42" 1.00 I 0.17 Control 5 0.11 I0.l3 v 0.87:0.17 Para-chlorophenylalanine 10 0.85 I 0.07 1.97 I 0.15"" 0.97 I 0.09 0.83 I 0.97" (2 4 hours) Control 5 0.18 I 0.12 1.50 I 0.13 0.51 I 0.05 .0.70 I 0.07 Para-chlorophenylalanine 10 0.84 i 0.11 2.20 10.20" 1.34 I 0.15"" 0.73 I 0.06" (48 50 hours) Control 5 0.19 I 0.20 1.19 I 0.13 0.42 I 0.08 0.61 I 0.12

50 EXAMPLE 1 [claim l. A method forenhancing libido in female domesticated animals for improved breeding purposes comprising administering to a domesticated female animal prior to breeding about 1 to about 250 mg/kg of a dopamine blocking agent selected from the group consisting of pimozide, fluspirilene and Spiroperidol.

2. A method for temporarily enhancing libido in animals comprising administering to an animal an effective amount of pimozide together with a suitable pharmaceutical carrier. 

1. A METHOD FOR ENHANCING LIBIDO IN FEMALE DOMESTICATED ANIMALS FOR IMPROVED BREEDING PURPOSES COMPRISING ADMINISTERING TO A DOMESTICATED FEMALE ANIMAL PRIOR TO BREEDING ABOUT 1 TO ABOUT 250 MG/KG OF A DOPAMINE BLOCKING AGENT SELECTED FROM THE GROUP CONSISTING OF PINOZIDE FLUSPIRILENE AND SPIROPERIDOL
 2. A method for temporarily enhancing libido in animals comprising administering to an animal an effective amount of pimozide together with a suitable pharmaceutical carrier. 